Induction of tanshinone 11 a on differentiation of human placenta-derived mesenchymal stem cells into cardiomyocytes and its mechanism / 吉林大学学报(医学版)

ABSTRACT

Objective: To investigate the induction of tanshinone [1 A (Tan fl A) on the differentiation of human placenta-derived mesenchymal stem cells (hPDMSCs) into cardiomyocytes, and to provide an experimental basis for Tan IT A as a cardiomyocytc differentiation inducer. McthodS; The hPDMSCs were treated with different concentrations of Tan Fl A (0.1.0.2.0.4.0.6.0.8.1.0. 2.0. 4.0. 6.0. 8.0. and 10. 0 mg • L ). and the nontoxic dose of Tan II A <0. 1 mg • L ) was scrccncd by MTT assay for experiment. The hPDMSCs were divided into control group. 5-aza induction (10 pmol • L ) group, and Tan Fl A induction (0. 1 mg • L ) group. After culture for 20 d. the expressions of o-sarcomeric acun (o-SCA) in the cells in various groups were detected with lmmunohistochcmastry; the positive expression rates of cardiac troponin 1 (cTnl) in the cells in various groups were detected with immunofluorescence, and the differentation rates of cardiomyocytes were calculated. The expression levels of GATA-binding protein 4 (GATA4). atnal natriuretic factor (ANF). cTnl. glycogen synthase kmase-30 (GSK-30 ) and 0-catemn in the cells were detected with Western blotting method. Results: The biological characteristics of hPDMSCs accorded with the mesenchymal stem cells. The MTT results showed that when the concentration of TanFl A was more than 0. 1 mg • L . the cell survival rates were decreased with the increase of concentrations the cells in control group showed a rapid growth trend before 12 d. and the proliferation activities of the cells began to decrease on the 12th day. Compared with control group, the cell activities in 5-aza induction group and TanFl A induction group were significantly decreased < P<0. 05). The immunohistochcmistry staining results showed that the cells in control group didn' t express a-SCA. and the cells in 5-aza induction group and TanFl A induction group expressed o-SCA. cspcaally in Tan Fl A induction group. Compared with control group, the expression levels of GAT A4 ( i - 2.937. P <0.05,4.769, P ,| , <0. 05) . ANF ( t -3.728. P <0.05 j r.-5.912, P ., ,<0.05). cTnl proteins in the cells in 5-aza induction group and Tan FI A induction group were significantly increased, and the expresson levels of (J-catcmn (t 2.985, P <0.05, l .1,-6.951, P .<0.05) protein were significantly decreased; compared with 5-aza induction group, the expresson levels of GATA4. ANF. and GSK-30 proteins in TanFl A induction group were increased < P<0. 05).

Conclusion:

Tan Fl A can induce the differentiation of hPDMSCs into cardiomyocytes. which has better effect than 5-aza. and its mechanism may be related to inhibiting the Wnt/|3-catcnin signaling pathway.